| Part ?Objective:To summarize the clinical characteristics,treatment landscape and outcome of patients with Waldenstrom's macroglobulinaemia(WM).Methods:We retrospectively collected clinical and laboratory data,treatment patterns,progression-free survival,and overall survival of WM patients in China.Newly diagnosed WM patients from 34 hospitals during January 2000 to December 2019 were enrolled in this observational study.Results:Among the 1170 patients,71.3%of patients manifest with anemia,16.8%with B symptoms and 38.6%with organomegaly or lymphadenopathy.The median age was 65 years with a male-to-female ratio of 2.62.As for complications,3.0%of patients presented with IgM related peripheral neuropathy and 3.0%of patients developed amyloidosis.Cryoglobulinemia was found in 0.9%of patients and cold agglutinin disease was 1.9%.1.2%of patients were diagnosed with Bing-Neel Syndrome at the time of diagnosis.11.9%of 895 patients received monotherapy,31.4%received chemoimmunotherapy and 56.7%received other combination regimens in the front-line therapy.The median progression-free survival after front-line therapy was 37 months.The median overall survival was 139 months with a median follow-up time of 20 months.According to the International Prognostic Scoring System,median OS of low-,intermediate-,and high-risk patients are unreached,unreached and 132 months,respectively(p=0.0149).In addition,the revised International Prognostic Scoring System could stratify patients into five different prognostic groups(P=0.0054)and the median OS of the very-low risk group and very-high risk group were unreached and 81 months respectively.In multivariate analyses;secondary amyloidosis(HR=2.991,95%CI 1.252-7.146,p 0.014),LDH?250IU/L(HR=1.910,95%CI 1.098-3.324,p=0.022),p 2MG?4mg/L(HR=1.725,95%CI 1.055-2.822,p=0.030)and PLT<100×109/L(HR=1.862,95%CI 1.151-3.012,p=0.011)were independent factors associated with worsened overall survival.Conclusions:The revised IPSSWM improved the risk stratification and prognosis assessment of WM patients.The treatment practice of WM has wide heterogeneity according to different clinical scenarios.Secondary amyloidosis,LDH?250IU/L,?2MG?4mg/L and PLT<100×109/L were associated with worsened overall survival.Part ?Objective:To unravel the tumor cell heterogeneity of Waldenstrom's macroglobulinaemia(WM).Methods:We performed single-cell RNA sequencing of CD 19+and CD19-CD38+cells of WM,IgM MGUS and healthy donors to profile the atlas of the composition and phenotype of CD 19+and CD 19-CD3 8+cells.Results:We found disease samples was composed of less early B-cell subsets and more CD8+CTL and NK cell population compared to healthy controls.We also identified a subpopulation of B cell with aberrant T cell antigens expression,and the trajectory analysis suggested that this abnormal subtype is the root cells.So,we posit that CD19+CD3+cells might be the cancer stem cells of WM.Compared with healthy donors,mature B cells of WM patient samples showed upregulated genes related to G-protein signaling and MHC class ?.Overexpression of T cell related genes was observed in IgM MGUS.IgM MGUS samples and WM samples both showed downregulated expression of metallothionein and heat shock protein family members.IgM MGUS patients have similar gene expression profile of plasma cells with WM patients.Conclusions:The findings give us comprehensive insights into tumor cell heterogeneity and provide strategies for novel therapy targets.B cell with aberrant T cell antigens expression might be cells with "stemness". |
PDF Full Text Request